Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1
Efficient antibiotics are being exhausted, which compromises the treatment of infections, including complicated skin and skin structure infections (cSSTI) often associated with multidrug resistant (MDR) bacteria, methicillin-resistant <i>S. aureus</i> (MRSA) being the most prevalent. Ant...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/11/1962 |
| _version_ | 1827675633943052288 |
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| author | Ana Gomes Lucinda J. Bessa Iva Fernandes Ricardo Ferraz Cláudia Monteiro M. Cristina L. Martins Nuno Mateus Paula Gameiro Cátia Teixeira Paula Gomes |
| author_facet | Ana Gomes Lucinda J. Bessa Iva Fernandes Ricardo Ferraz Cláudia Monteiro M. Cristina L. Martins Nuno Mateus Paula Gameiro Cátia Teixeira Paula Gomes |
| author_sort | Ana Gomes |
| collection | DOAJ |
| description | Efficient antibiotics are being exhausted, which compromises the treatment of infections, including complicated skin and skin structure infections (cSSTI) often associated with multidrug resistant (MDR) bacteria, methicillin-resistant <i>S. aureus</i> (MRSA) being the most prevalent. Antimicrobial peptides (AMP) are being increasingly regarded as the new hope for the post-antibiotic era. Thus, future management of cSSTI may include use of peptides that, on the one hand, behave as AMP and, on the other, are able to promote fast and correct skin rebuilding. As such, we combined the well-known cosmeceutical pentapeptide-4 (PP4), devoid of antimicrobial action but possessing collagenesis-boosting properties, with the AMP 3.1, to afford the chimeric peptide PP4-3.1. We further produced its <i>N</i>-methyl imidazole derivative, MeIm-PP4-3.1. Both peptide-based constructs were evaluated in vitro against Gram-negative bacteria, Gram-positive bacteria, and <i>Candida</i> spp. fungi. Additionally, the antibiofilm activity, the toxicity to human keratinocytes, and the activity against <i>S. aureus</i> in simulated wound fluid (SWF) were assessed. The chimeric peptide PP4-3.1 stood out for its potent activity against Gram-positive and Gram-negative bacteria, including against MDR clinical isolates (0.8 ≤ MIC ≤ 5.7 µM), both in planktonic form and in biofilm matrix. The peptide was also active against three clinically relevant species of <i>Candida</i> fungi, with an overall performance superior to that of fluconazole. Altogether, data reveal that PP4-3.1 is as a promising lead for the future development of new topical treatments for severe skin infections. |
| first_indexed | 2024-03-10T05:08:41Z |
| format | Article |
| id | doaj.art-21a17009bb9a4983853fc37a7b9b30ca |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T05:08:41Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-21a17009bb9a4983853fc37a7b9b30ca2023-11-23T01:00:21ZengMDPI AGPharmaceutics1999-49232021-11-011311196210.3390/pharmaceutics13111962Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1Ana Gomes0Lucinda J. Bessa1Iva Fernandes2Ricardo Ferraz3Cláudia Monteiro4M. Cristina L. Martins5Nuno Mateus6Paula Gameiro7Cátia Teixeira8Paula Gomes9LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, P-4169-007 Porto, PortugalLAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, P-4169-007 Porto, PortugalLAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, P-4169-007 Porto, PortugalLAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, P-4169-007 Porto, Portugali3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, P-4200-135 Porto, Portugali3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, P-4200-135 Porto, PortugalLAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, P-4169-007 Porto, PortugalLAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, P-4169-007 Porto, PortugalLAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, P-4169-007 Porto, PortugalLAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, P-4169-007 Porto, PortugalEfficient antibiotics are being exhausted, which compromises the treatment of infections, including complicated skin and skin structure infections (cSSTI) often associated with multidrug resistant (MDR) bacteria, methicillin-resistant <i>S. aureus</i> (MRSA) being the most prevalent. Antimicrobial peptides (AMP) are being increasingly regarded as the new hope for the post-antibiotic era. Thus, future management of cSSTI may include use of peptides that, on the one hand, behave as AMP and, on the other, are able to promote fast and correct skin rebuilding. As such, we combined the well-known cosmeceutical pentapeptide-4 (PP4), devoid of antimicrobial action but possessing collagenesis-boosting properties, with the AMP 3.1, to afford the chimeric peptide PP4-3.1. We further produced its <i>N</i>-methyl imidazole derivative, MeIm-PP4-3.1. Both peptide-based constructs were evaluated in vitro against Gram-negative bacteria, Gram-positive bacteria, and <i>Candida</i> spp. fungi. Additionally, the antibiofilm activity, the toxicity to human keratinocytes, and the activity against <i>S. aureus</i> in simulated wound fluid (SWF) were assessed. The chimeric peptide PP4-3.1 stood out for its potent activity against Gram-positive and Gram-negative bacteria, including against MDR clinical isolates (0.8 ≤ MIC ≤ 5.7 µM), both in planktonic form and in biofilm matrix. The peptide was also active against three clinically relevant species of <i>Candida</i> fungi, with an overall performance superior to that of fluconazole. Altogether, data reveal that PP4-3.1 is as a promising lead for the future development of new topical treatments for severe skin infections.https://www.mdpi.com/1999-4923/13/11/1962antibacterialantibiofilmantifungalantimicrobial peptidescollagenmultidrug resistance |
| spellingShingle | Ana Gomes Lucinda J. Bessa Iva Fernandes Ricardo Ferraz Cláudia Monteiro M. Cristina L. Martins Nuno Mateus Paula Gameiro Cátia Teixeira Paula Gomes Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1 Pharmaceutics antibacterial antibiofilm antifungal antimicrobial peptides collagen multidrug resistance |
| title | Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1 |
| title_full | Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1 |
| title_fullStr | Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1 |
| title_full_unstemmed | Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1 |
| title_short | Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1 |
| title_sort | disclosure of a promising lead to tackle complicated skin and skin structure infections antimicrobial and antibiofilm actions of peptide pp4 3 1 |
| topic | antibacterial antibiofilm antifungal antimicrobial peptides collagen multidrug resistance |
| url | https://www.mdpi.com/1999-4923/13/11/1962 |
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