Amyloid peptides with antimicrobial and/or microbial agglutination activity

Abstract

Microbe (including bacteria, fungi, and virus) infection in brains is associated with amyloid fibril deposit and neurodegeneration. Increasing findings suggest that amyloid proteins, like Abeta (Aβ), are important innate immune effectors in preventing infections. In some previous studies, amyloid peptides have been linked to antimicrobial peptides due to their common mechanisms in membrane-disruption ability, while the other mechanisms of bactericidal protein aggregation and protein function knockdown are less discussed. Besides, another important function of amyloid peptides in pathogen agglutination is rarely illustrated. In this review, we summarized and divided the different roles and mechanisms of amyloid peptides against microbes in antimicrobial activity and microbe agglutination activity. Besides, the range of amyloids’ antimicrobial spectrum, the effectiveness of amyloid peptide states (monomers, oligomers, and fibrils), and cytotoxicity are discussed. The good properties of amyloid peptides against microbes might provide implications for the development of novel antimicrobial drug. Key points • Antimicrobial and/or microbial agglutination is a characteristic of amyloid peptides. • Various mechanisms of amyloid peptides against microbes are discovered recently . • Amyloid peptides might be developed into novel antimicrobial drugs . Supplementary information The online version contains supplementary material available at 10.1007/s00253-022-12246-w.

The morphology and structural features of self-aggregating hexapeptides with antibiofilm formation activity

“…However, very few synthetic self-aggregating peptides have been found to exert agglutination functions without bacteriacidal effects up to now. 9,10,29,30 As far as we know, self-aggregating hexapeptides are the shortest peptides with simple microbes agglutination functions and antibiofilm-formation activities. In our opinion, there might be numerous amyloid peptides with microbes agglutination activities that have not been revealed yet.…”

Dementia, infections and vaccines: 30 years of controversy

“…Antimicrobials may exert their action either by directly killing invasive pathogens, or via immune modulation by penetrating the cells, raising the perspective of numerous possibilities that could be harnessed to stop or decrease viral or bacterial invasion, with a resultant effect on neuroinflammation. Very recent evidence indicates that amyloid peptides display functional roles against microbes not only via antimicrobial function (membrane disruption, protein aggregation or altered protein conformation within the microbe) but also via microbe agglutination function [ 45 ]. Amyloid beta peptides can form or initiate biofilm formation, sequestering and neutralizing the microbes.…”

How do Antimicrobial Peptides Interact with the Outer Membrane of Gram-Negative Bacteria? Role of Lipopolysaccharides in Peptide Binding, Anchoring, and Penetration

“…However, some AMPs cross the membrane and enter the cell. The intracellular activity of AMPs involves their binding to either DNA or proteins. − AMPs are short, positively charged peptides that are characterized by large conformational flexibility and usually have an undefined secondary structure in water. Electrostatic interactions constitute the driving force for anchoring the AMPs on the membrane surface. ,, Membrane-associated AMPs interact with the lipid molecules, inserting themselves into the hydrophobic membrane fragment while undergoing a conformational transformation stabilizing α-helical, β-sheet, or extended secondary structure motifs. − Inserted AMPs disrupt the phospholipid membrane through the formation of pores, channels, or lipid–peptide micelles. − Due to experimental difficulties in the fabrication of models of microbial cell membranes, most of the earlier studies on the action of AMPs were done on phospholipid bilayers, which only remotely resemble models of bacterial cell envelopes.…”

“…Recent studies show that amyloid peptides and β-hairpin AMPs, capable of self-assembly into fibrils, are potent antimicrobial agents. A strong electrostatic binding of AMPs to lipopolysaccharides reduces the peptide mobility, leading to its accumulation in the OM region, which, by agglutination, eventually induces bacterial cell death. , The lack of clarity on the action of AMPs on lipopolysaccharides in the OM calls for an in-depth analysis of the underlying molecular interactions.…”

“…Agglutination was proposed as another possible pathway of AMPs' action on the bacterial membranes. 9,46,48 Recent studies show that amyloid peptides 9 and β-hairpin AMPs, 48 capable of self-assembly into fibrils, are potent antimicrobial agents. A strong electrostatic binding of AMPs to lipopolysaccharides reduces the peptide mobility, leading to its accumulation in the OM region, which, by agglutination, eventually induces bacterial cell death.…”