Amyloids were first observed in the year 1639, by Nicolas Fontanus. However, the term amyloid, meaning “similarity with starch” was coined two centuries later as they stain with dye Congo red in a similar way as did cellulose and starch. Amyloid is a substance that appears homogeneous and amorphous under the light microscope and produces an apple-green birefringence under polarized light upon staining with Congo red. It was only until 20th century the chemical analysis revealed that amyloids are composed of proteins and not starch.
Structural Characteristics of Amyloids
Structural conversion of soluble proteins to self-associating conformations leads to formation of amyloids. They are macromolecular insoluble fibrillar aggregates that are formed during the process of protein folding and are linked to the onset of various human neurodegenerative disorders like Alzheimer’s or Parkinson’s diseases. But, amyloids are not always associated with pathogenesis, rather amyloids are found to be functional in some microbes e.g. bacteria. They are termed as functional amyloids to differentiate them from the harmful amyloids due to the fact that amyloid fibers had always been associated with human pathologies.
Amyloid proteins vary widely with respect to their amino acid sequences, despite having similarities in their quaternary structure. Under electron microscopy, amyloid appears to be rigid, linear, aggregated fibrils that are 7.5-10.0 nm in width and of indefinite length. These fibrils are insoluble and generally resist proteolytic digestion. X ray crystallography reveals that β-amyloid proteins of Alzheimer’s disease are enriched in β-sheets arranged perpendicular to the axis of the fiber.
Amyloids in Bacteria
Unlike humans, amyloids perform various physiological functions in bacteria. For example, chaplins of Streptomyces coelicolor help in the rising of the aerial hyphae thereby interacting with surfaces. In Mycobacterium tuberculosis, amyloid pili (MTP) interacts with the host during pathogenesis. Another example of functional amyloid includes the harpin Hpag of Xanthomonas which form amyloid fibers in vitro, and is related to the hypersensitive response (HR) caused in the host. Curli generated by Escherichia coli and Salmonella spp., chaplins formed by Streptomyces spp., and TasA fibers produced by Bacillus subtilis are all functional amyloids produced by microbes to promote interbacterial interactions. Thus, majority of functional amyloids in bacteria perform physiological tasks on the cell surface such as biofilm formation, adhesion, invasion of host cells, and host–pathogen interactions.
| Species | Protein | Function |
| Humans | Pmel17 | Elimination of toxic intermediates during melanin synthesis |
| Fungi | Hydrophobins | Formation of fungal coat |
| Escherichia coli, Salmonella enteritidis | Curli | Interaction with host, biofilm formation |
| Pseudomonas sp. | FapC | Biofilm formation |
| Streptomyces coelicolor | Chaplins | Formation of aerial structures |
| Bacillus subtilis | TasA | Biofilm formation |
| Klebsiella pneumoniae | Microcin E492 | Antimicrobial |
| Staphylococcus aureus | PSM | Biofilm formation |
| Streptococcus mutans | Adhesin P1 | Biofilm formation |
| Mycobacterium tuberculosis | MTP | Host interaction |
| Xanthomonas axonopodis | Harpin | Virulence factor, multicellularity |
Bacteria secrete peptides called PSM (phenol-soluble modulins) which perform varied functions e.g. stimulate inflammatory responses, lyse human cells, and contribute to biofilm structuring. PSMα3 is virulent 22-residue amyloid peptides secreted by Staphylococcus aureus which assembles into amyloids that help the bacteria kill other cells.
Earlier, PSMα3 clusters were assumed to be like any other amyloid. But researchers using X-ray crystallography found an unexpected departure from the common amyloid cross-β folded architecture. Instead, PSMα3 forms amphipathic α-helices that are folded to stack perpendicular to the fibril axis into sheets. This unusual cross-α structure was important for amyloid fibril toxicity. This goes completely against the cross-β amyloid structure of Aβ peptide (Alzeihmer’s) or α-Syn peptide (Parkinson’s) structure during pathogenesis. PSMα3 fiber was found to be made up of curly structures called alpha helices resembling an old-fashioned phone cord.
Conclusion
The importance of amyloid fibers lies in the fact that they represent interesting targets for the search of new therapies that contribute to the fight of bacterial biofilms and the biochemical problems they may cause. They help us in providing a formidable tool for the search of molecules that can be exploited in two directions: anti-biofilm and anti-amyloid.
References
- Functional amyloids in bacteria. In: International Microbiology [2014] 17: 65-73.
- Amyloid Formation in Bacteria. In: Roberts G.C.K. (eds) Encyclopedia of Biophysics. Springer, Berlin, Heidelberg [2013].
- Bacteria’s amyloids display surprising structure, In: Science News [2017] February 23.
- The cytotoxic Staphylococcus aureus PSMα3 reveals a cross-α amyloid-like fibril. In: Science [2017] 355: 831-833.
- Bacterial Amyloids. In: Methods in Molecular Biology [2012] 849: 303–320.
