Optimizing Antimicrobial Peptide Design: Integration of Cell-Penetrating Peptides, Amyloidogenic Fragments, and Amino Acid Residue Modifications

• Published in: International journal of molecular sciences 2024-06, Vol.25 (11), p.6030
• Main Authors: Kravchenko, Sergey V, Domnin, Pavel A, Grishin, Sergei Y, Zakhareva, Alena P, Zakharova, Anastasiia A, Mustaeva, Leila G, Gorbunova, Elena Y, Kobyakova, Margarita I, Surin, Alexey K, Poshvina, Darya V, Fadeev, Roman S, Azev, Viacheslav N, Ostroumova, Olga S, Ermolaeva, Svetlana A, Galzitskaya, Oxana V
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acids - chemistry; Amyloidogenic Proteins - chemistry; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial agents; Antimicrobial Peptides - chemistry; Antimicrobial Peptides - pharmacology; Bacteria; Cell-Penetrating Peptides - chemistry; Cell-Penetrating Peptides - pharmacology; Design; Drug Design; Drug resistance; Drug resistance in microorganisms; Drug therapy; E coli; Gram-negative bacteria; Gram-positive bacteria; Homeopathy; Materia medica and therapeutics; Methicillin; Microbial Sensitivity Tests; Microorganisms; Multidrug resistant organisms; Pathogens; Peptides; Proteins; Therapeutics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25116030

The escalating threat of multidrug-resistant pathogens necessitates innovative approaches to combat infectious diseases. In this study, we examined peptides R23F *, V31K *, and R44K *, which were engineered to include an amyloidogenic fragment sourced from the S1 protein of , along with one or two cell-penetrating peptide (CPP) components. We assessed the antimicrobial efficacy of these peptides in a liquid medium against various strains of both Gram-positive bacteria, including (209P and 129B strains), MRSA (SA 180 and ATCC 43300 strains), and (strain IP 5832), and Gram-negative bacteria such as (ATCC 28753 and 2943 strains) and (MG1655 and K12 strains). Peptides R23F *, V31K *, and R44K * exhibited antimicrobial activity comparable to gentamicin and meropenem against all tested bacteria at concentrations ranging from 24 to 48 μM. The peptides showed a stronger antimicrobial effect against . Notably, peptide R44K * displayed high efficacy compared to peptides R23F * and V31K *, particularly evident at lower concentrations, resulting in significant inhibition of bacterial growth. Furthermore, modified peptides V31K * and R44K * demonstrated enhanced inhibitory effects on bacterial growth across different strains compared to their unmodified counterparts V31K and R44K . These results highlight the potential of integrating cell-penetrating peptides, amyloidogenic fragments, and amino acid residue modifications to advance the innovation in the field of antimicrobial peptides, thereby increasing their effectiveness against a broad spectrum of pathogens.