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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Autores principales:	Ana Gomes, Lucinda J. Bessa, Iva Fernandes, Ricardo Ferraz, Cláudia Monteiro, M. Cristina L. Martins, Nuno Mateus, Paula Gameiro, Cátia Teixeira, Paula Gomes
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	antibacterial antibiofilm antifungal antimicrobial peptides collagen multidrug resistance Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/21a17009bb9a4983853fc37a7b9b30ca
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spelling	oai:doaj.org-article:21a17009bb9a4983853fc37a7b9b30ca2021-11-25T18:42:24ZDisclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.110.3390/pharmaceutics131119621999-4923https://doaj.org/article/21a17009bb9a4983853fc37a7b9b30ca2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1962https://doaj.org/toc/1999-4923Efficient 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.Ana GomesLucinda J. BessaIva FernandesRicardo FerrazCláudia MonteiroM. Cristina L. MartinsNuno MateusPaula GameiroCátia TeixeiraPaula GomesMDPI AGarticleantibacterialantibiofilmantifungalantimicrobial peptidescollagenmultidrug resistancePharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1962, p 1962 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibacterial antibiofilm antifungal antimicrobial peptides collagen multidrug resistance Pharmacy and materia medica RS1-441
spellingShingle	antibacterial antibiofilm antifungal antimicrobial peptides collagen multidrug resistance Pharmacy and materia medica RS1-441 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
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.
format	article
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
title	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_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_sort	disclosure of a promising lead to tackle complicated skin and skin structure infections: antimicrobial and antibiofilm actions of peptide pp4-3.1
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/21a17009bb9a4983853fc37a7b9b30ca
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Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1

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