Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of <i>P. aeruginosa</i>?
The development and testing of new antimicrobial peptides (AMPs) represent an important milestone toward the development of new antimicrobial drugs that can inhibit the growth of pathogens and multidrug-resistant microorganisms such as <i>Pseudomonas aeruginosa,</i> Gram-negative bacteri...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9776 |
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| author | Sergei Y. Grishin Pavel A. Domnin Sergey V. Kravchenko Viacheslav N. Azev Leila G. Mustaeva Elena Y. Gorbunova Margarita I. Kobyakova Alexey K. Surin Maria A. Makarova Stanislav R. Kurpe Roman S. Fadeev Alexey S. Vasilchenko Victoria V. Firstova Svetlana A. Ermolaeva Oxana V. Galzitskaya |
| author_facet | Sergei Y. Grishin Pavel A. Domnin Sergey V. Kravchenko Viacheslav N. Azev Leila G. Mustaeva Elena Y. Gorbunova Margarita I. Kobyakova Alexey K. Surin Maria A. Makarova Stanislav R. Kurpe Roman S. Fadeev Alexey S. Vasilchenko Victoria V. Firstova Svetlana A. Ermolaeva Oxana V. Galzitskaya |
| author_sort | Sergei Y. Grishin |
| collection | DOAJ |
| description | The development and testing of new antimicrobial peptides (AMPs) represent an important milestone toward the development of new antimicrobial drugs that can inhibit the growth of pathogens and multidrug-resistant microorganisms such as <i>Pseudomonas aeruginosa,</i> Gram-negative bacteria. Most AMPs achieve these goals through mechanisms that disrupt the normal permeability of the cell membrane, which ultimately leads to the death of the pathogenic cell. Here, we developed a unique combination of a membrane penetrating peptide and peptides prone to amyloidogenesis to create hybrid peptide: “cell penetrating peptide + linker + amyloidogenic peptide”. We evaluated the antimicrobial effects of two peptides that were developed from sequences with different propensities for amyloid formation. Among the two hybrid peptides, one was found with antibacterial activity comparable to antibiotic gentamicin sulfate. Our peptides showed no toxicity to eukaryotic cells. In addition, we evaluated the effect on the antimicrobial properties of amino acid substitutions in the non-amyloidogenic region of peptides. We compared the results with data on the predicted secondary structure, hydrophobicity, and antimicrobial properties of the original and modified peptides. In conclusion, our study demonstrates the promise of hybrid peptides based on amyloidogenic regions of the ribosomal S1 protein for the development of new antimicrobial drugs against <i>P. aeruginosa</i>. |
| first_indexed | 2024-03-10T07:36:11Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:36:11Z |
| publishDate | 2021-09-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d9e0cb03cf0c4415a055197df5947c5e2023-11-22T13:27:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218977610.3390/ijms22189776Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of <i>P. aeruginosa</i>?Sergei Y. Grishin0Pavel A. Domnin1Sergey V. Kravchenko2Viacheslav N. Azev3Leila G. Mustaeva4Elena Y. Gorbunova5Margarita I. Kobyakova6Alexey K. Surin7Maria A. Makarova8Stanislav R. Kurpe9Roman S. Fadeev10Alexey S. Vasilchenko11Victoria V. Firstova12Svetlana A. Ermolaeva13Oxana V. Galzitskaya14Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, RussiaGamaleya Research Centre of Epidemiology and Microbiology, 123098 Moscow, RussiaInstitute of Environmental and Agricultural Biology (X-BIO), Tyumen State University, 625003 Tyumen, RussiaThe Branch of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, 142290 Pushchino, RussiaThe Branch of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, 142290 Pushchino, RussiaThe Branch of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, 142290 Pushchino, RussiaInstitute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, RussiaInstitute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, RussiaState Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaInstitute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, RussiaInstitute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, RussiaInstitute of Environmental and Agricultural Biology (X-BIO), Tyumen State University, 625003 Tyumen, RussiaState Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, RussiaGamaleya Research Centre of Epidemiology and Microbiology, 123098 Moscow, RussiaInstitute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, RussiaThe development and testing of new antimicrobial peptides (AMPs) represent an important milestone toward the development of new antimicrobial drugs that can inhibit the growth of pathogens and multidrug-resistant microorganisms such as <i>Pseudomonas aeruginosa,</i> Gram-negative bacteria. Most AMPs achieve these goals through mechanisms that disrupt the normal permeability of the cell membrane, which ultimately leads to the death of the pathogenic cell. Here, we developed a unique combination of a membrane penetrating peptide and peptides prone to amyloidogenesis to create hybrid peptide: “cell penetrating peptide + linker + amyloidogenic peptide”. We evaluated the antimicrobial effects of two peptides that were developed from sequences with different propensities for amyloid formation. Among the two hybrid peptides, one was found with antibacterial activity comparable to antibiotic gentamicin sulfate. Our peptides showed no toxicity to eukaryotic cells. In addition, we evaluated the effect on the antimicrobial properties of amino acid substitutions in the non-amyloidogenic region of peptides. We compared the results with data on the predicted secondary structure, hydrophobicity, and antimicrobial properties of the original and modified peptides. In conclusion, our study demonstrates the promise of hybrid peptides based on amyloidogenic regions of the ribosomal S1 protein for the development of new antimicrobial drugs against <i>P. aeruginosa</i>.https://www.mdpi.com/1422-0067/22/18/9776ribosomal S1 proteinamyloidantimicrobial peptides<i>Pseudomonas aeruginosa</i>cell penetrating peptide |
| spellingShingle | Sergei Y. Grishin Pavel A. Domnin Sergey V. Kravchenko Viacheslav N. Azev Leila G. Mustaeva Elena Y. Gorbunova Margarita I. Kobyakova Alexey K. Surin Maria A. Makarova Stanislav R. Kurpe Roman S. Fadeev Alexey S. Vasilchenko Victoria V. Firstova Svetlana A. Ermolaeva Oxana V. Galzitskaya Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of <i>P. aeruginosa</i>? International Journal of Molecular Sciences ribosomal S1 protein amyloid antimicrobial peptides <i>Pseudomonas aeruginosa</i> cell penetrating peptide |
| title | Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of <i>P. aeruginosa</i>? |
| title_full | Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of <i>P. aeruginosa</i>? |
| title_fullStr | Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of <i>P. aeruginosa</i>? |
| title_full_unstemmed | Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of <i>P. aeruginosa</i>? |
| title_short | Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of <i>P. aeruginosa</i>? |
| title_sort | is it possible to create antimicrobial peptides based on the amyloidogenic sequence of ribosomal s1 protein of i p aeruginosa i |
| topic | ribosomal S1 protein amyloid antimicrobial peptides <i>Pseudomonas aeruginosa</i> cell penetrating peptide |
| url | https://www.mdpi.com/1422-0067/22/18/9776 |
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