Enhancing the Antimicrobial Properties of Peptides through Cell-Penetrating Peptide Conjugation: A Comprehensive Assessment
Year: 2023
Type: article
Abstract: Combining antimicrobial peptides (AMPs) with cell-penetrating peptides (CPPs) has shown promise in boosting antimicrobial potency, especially against Gram-negative bacteria. We examined the CPP-AMP interaction with distinct bacterial types based on cell wall differences. Our investigation focused on AMPs incorporating penetratin CPP and dihybrid peptides containing both cell-penetrating TAT protein fragments from the human immunodeficiency virus and Antennapedia peptide (Antp). Assessment of the peptides TAT-AMP, AMP-Antp, and TAT-AMP-Antp revealed their potential against Gram-positive strains (Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), and Bacillus cereus). Peptides TAT-AMP and AMP-Antp using an amyloidogenic AMP from S1 ribosomal protein Thermus thermophilus, at concentrations ranging from 3 to 12 μM, exhibited enhanced antimicrobial activity against B. cereus. TAT-AMP and TAT-AMP-Antp, using an amyloidogenic AMP from the S1 ribosomal protein Pseudomonas aeruginosa, at a concentration of 12 µM, demonstrated potent antimicrobial activity against S. aureus and MRSA. Notably, the TAT-AMP, at a concentration of 12 µM, effectively inhibited Escherichia coli (E. coli) growth and displayed antimicrobial effects similar to gentamicin after 15 h of incubation. Peptide characteristics determined antimicrobial activity against diverse strains. The study highlights the intricate relationship between peptide properties and antimicrobial potential. Mechanisms of AMP action are closely tied to bacterial cell wall attributes. Peptides with the TAT fragment exhibited enhanced antimicrobial activity against S. aureus, MRSA, and P. aeruginosa. Peptides containing only the Antp fragment displayed lower activity. None of the investigated peptides demonstrated cytotoxic or cytostatic effects on either BT-474 cells or human skin fibroblasts. In conclusion, CPP-AMPs offer promise against various bacterial strains, offering insights for targeted antimicrobial development.
Authors: Sergey V. Kravchenko, Pavel A. Domnin, Sergei Y. Grishin, Nikita A. Vershinin, Elena V. Gurina, Anastasiia A. Zakharova, Viacheslav N. Azev, Leila G. Mustaeva, Elena Y. Gorbunova, Margarita I. Kobyakova, Alexey K. Surin, Roman S. Fadeev, Olga S. Ostroumova, Svetlana A. Ermolaeva, Oxana V. Galzitskaya
Institutions: University of Tyumen, Lomonosov Moscow State University, Gamalei Institute of Epidemiology and Microbiology, Russian Academy of Sciences, Institute of Protein Research, Institute of Cytology, Institute of Bioorganic Chemistry, Institute of Theoretical and Experimental Biophysics, Institute of Cytology and Genetics, Institute of Clinical and Experimental Lymphology, State Research Center for Applied Microbiology and Biotechnology
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,780
Funder: Russian Science Foundation
Award: G1816318948
OpenAlex ID: W4388970973