Enhancing the Antimicrobial Properties of Peptides through Cell-Penetrating Peptide Conjugation: A Comprehensive Assessment
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Published:2023-11-24
Issue:23
Volume:24
Page:16723
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Kravchenko Sergey V.1ORCID, Domnin Pavel A.23, Grishin Sergei Y.14ORCID, Vershinin Nikita A.1, Gurina Elena V.1, Zakharova Anastasiia A.5, Azev Viacheslav N.6ORCID, Mustaeva Leila G.6, Gorbunova Elena Y.6, Kobyakova Margarita I.78ORCID, Surin Alexey K.469, Fadeev Roman S.7, Ostroumova Olga S.5, Ermolaeva Svetlana A.3ORCID, Galzitskaya Oxana V.47ORCID
Affiliation:
1. Institute of Environmental and Agricultural Biology (X-BIO), Tyumen State University, 625003 Tyumen, Russia 2. Biology Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia 3. Gamaleya Research Centre of Epidemiology and Microbiology, 123098 Moscow, Russia 4. Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Russia 5. Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia 6. The Branch of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, 142290 Pushchino, Russia 7. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia 8. Research Institute of Clinical and Experimental Lymphology—Branch of the Institute of Cytology and Genetics Siberian Branch of Russian Academy of Sciences, 630060 Novosibirsk, Russia 9. State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia
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.
Funder
state assignment 2019
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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