Multiple Antimicrobial Effects of Hybrid Peptides Synthesized Based on the Sequence of Ribosomal S1 Protein from Staphylococcus aureus

Abstract

The need to develop new antimicrobial peptides is due to the high resistance of pathogenic bacteria to traditional antibiotics now and in the future. The creation of synthetic peptide constructs is a common and successful approach to the development of new antimicrobial peptides. In this work, we use a simple, flexible, and scalable technique to create hybrid antimicrobial peptides containing amyloidogenic regions of the ribosomal S1 protein from Staphylococcus aureus. While the cell-penetrating peptide allows the peptide to enter the bacterial cell, the amyloidogenic site provides an antimicrobial effect by coaggregating with functional bacterial proteins. We have demonstrated the antimicrobial effects of the R23F, R23DI, and R23EI hybrid peptides against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, and Bacillus cereus. R23F, R23DI, and R23EI can be used as antimicrobial peptides against Gram-positive and Gram-negative bacteria resistant to traditional antibiotics.

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

“…Our study showed that Sarmodified peptides exhibit a wide range of antimicrobial activity against MRSA, P. aeruginosa, E. coli, and B. cereus [36]. As a result of the series of experiments, the minimum inhibitory concentrations (MICs) of the modified peptides were determined against strains of pathogenic methicillin-resistant S. aureus (MRSA), S. aureus, and P. aeruginosa (Table 2) [35,36]. As follows from Table 2, we found that the antimicrobial effect of the same peptides against various pathogenic microorganisms is comparable to the MIC (~1-5 µM) of the commercial antibiotic gentamicin sulfate [116,117].…”

“…In addition, modified peptides can provide a longer duration of action, as they are more resistant to proteases. Our study showed that Sarmodified peptides exhibit a wide range of antimicrobial activity against MRSA, P. aeruginosa, E. coli, and B. cereus [36]. As a result of the series of experiments, the minimum inhibitory concentrations (MICs) of the modified peptides were determined against strains of pathogenic methicillin-resistant S. aureus (MRSA), S. aureus, and P. aeruginosa (Table 2) [35,36].…”

“…Additionally, the possibility of changing the peptide template makes it possible to introduce various modifications that modulate antimicrobial activity, tissue specificity, toxicity, and other types of biological activity. Note that the peptides synthesized by us are non-toxic for human fibroblast cells [35,36]. The greater resistance of amyloidogenic sequences to proteolysis is an additional advantage of amyloidogenic antimicrobial peptides, due to the fact that they are more stable.…”

“…Alignment of the gene sequences in this group shows a percentage identity of 53% for some records, for records with high protein sequence identity, the gene identity is 99-100%. Note that in this group there is a strain MRSA252 (UniProt ID: Q6GGT5) in which residue 281Asp is located in the position of the corresponding amyloidogenic region [36] in place of 281Val in the strain MSSA476 (UniProt ID: Q6G987). For strain MRSA252 in the S1 protein sequence, substitution 370Ser is also characteristic in comparison with strain MSSA476, strain N315, strain MW2, and strain Mu50/ATCC700699 (370N).…”

“…The design of peptides based on hot spot aggregation assumed a duplicate APR sequence flanked at the edges of the chain by arginine R-APR-RR to prevent aggregation and increase the absorption capacity of the bacterial cell. In our studies, we constructed a peptide capable of specifically binding to a unique target by the directed co-aggregation mechanism [33][34][35][36]. To do this, we selected APR regions in the target protein sequence using the FoldAmyloid [37], PASTA 2.0 [38], Waltz [39], and AGGRESCAN [40] programs, taking into account the regions predicted by most programs.…”