Amyloidogenic Peptides: New Class of Antimicrobial Peptides with the Novel Mechanism of Activity

Abstract

Antibiotic-resistant bacteria are recognized as one of the leading causes of death in the world. We proposed and successfully tested peptides with a new mechanism of antimicrobial action “protein silencing” based on directed co-aggregation. The amyloidogenic antimicrobial peptide (AAMP) interacts with the target protein of model or pathogenic bacteria and forms aggregates, thereby knocking out the protein from its working condition. In this review, we consider antimicrobial effects of the designed peptides on two model organisms, E. coli and T. thermophilus, and two pathogenic organisms, P. aeruginosa and S. aureus. We compare the amino acid composition of proteomes and especially S1 ribosomal proteins. Since this protein is inherent only in bacterial cells, it is a good target for studying the process of co-aggregation. This review presents a bioinformatics analysis of these proteins. We sum up all the peptides predicted as amyloidogenic by several programs and synthesized by us. For the four organisms we studied, we show how amyloidogenicity correlates with antibacterial properties. Let us especially dwell on peptides that have demonstrated themselves as AMPs for two pathogenic organisms that cause dangerous hospital infections, and in which the minimal inhibitory concentration (MIC) turned out to be comparable to the MIC of gentamicin sulfate. All this makes our study encouraging for the further development of AAMP. The hybrid peptides may thus provide a starting point for the antibacterial application of amyloidogenic peptides.

Helical intermediate formation and its role in amyloids of an amphibian antimicrobial peptide

“…Therefore, it can be used as a model peptide to study the amyloid formation and antimicrobial drug development. [53][54][55] The roles…”

Biological Activity of Cyclic Peptide Extracted from Sphaeranthus amaranthoides Using De Novo Sequencing Strategy by Mass Spectrometry for Cancer

“…The disorganization of the mitochondrial membrane when transferred to the cancer cells leads to programmed cell death. Moreover, the aliphatic index, protein binding interaction potential, and hydrophobicity of the peptides were estimated using the tool in the APD3 (an antimicrobial peptide database) [ 16 ]. A Basic Local Alignment Search Tool (BLAST) for protein (BLASTP) was performed against the protein sequence of the herbaceous (temperate herbaceous clade (taxid: 2233839)) database to predict the class of the novel peptides.…”

“…The amino acid composition plays an important role in the AntiCP web server. It is a user-friendly web server [ 16 ]. Furthermore, the 3D structure of the peptides was obtained using PEPstrMOD.…”

Bioinformatics study of the family of bacterial ribosomal proteins S1: features of structural organization, amyloidogenic regions in S1 domains, evolution of bacterial phyla, creation of new antibacterial peptides

“…Анализ частоты распределения амилоидогенных областей в доменах S1 позволил выявить характерные особенности для каждого отдельного S1 домена [23]…”